FDA highlights new requirements for second-generation BMS

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Washington, DC.—The FDA released updated guidelines for second-generation bare-metal stents (BMS) to reflect its current recommendations, incorporating changes, such as design alterations and clinical trialing expectations, from the previous guidance released four years prior, according to Katherine J. Fronczak, an FDA representative who presented the data here last week at the Cardiovascular Research Therapies (CRT) 2009 conference.

The agency has added a section on the stent and its delivery system, which is "similar to the simulated use method outlined in the DES guidance documents," she said. The FDA also added recommendations for additional bench-testing for stents intended for in-stent restenosis and bifurcation indications.

The agency added several delivery system tests and updated its nomenclature, "making the document consistent with PTCA [percutaneous transluminal coronary angioplasty] catheters," Franczak noted. In addition, the revisions include shelf-life section, which lists all the bench-testing that the agency believes should be repeated for aged devices to support shelf-life indications.

Also newly highlighted are more specific recommendations about various types of corrosion evaluations. For strut/strain analysis, Fronczak said that the agency added more detailed recommendations regarding computational model, as well as physiologic loading conditions, "which represent what can be expected during clinical use. This includes overlapping stents and tortuous vessels." She said that the guidance includes more detailed recommendations for the presentation of these results.

Similarly, the accelerated durability testing section has been updated to recommend evaluation of overlapping stents in mock vessels, simulating the expected worse case anatomical conditions.

Other revisions include new recommendations for radiofrequency heating stents and an MRI section that reflects the most recent 2008 MRI guidance.

The agency also added "testing considerations to the biocompatibility section, based on the most common deficiencies that have arisen in our reviews," Fronczak said.

In regards to BMS clinical trial design, Fronczak said that the FDA "believes that there is sufficient experience with BMS to allow a non-randomized, multicenter, single-arm study." The agency also purports that the use of a performance goal in these studies is acceptable as a control arm. However, she said that the FDA asks that researchers adhere to the following expectations when driving a performance goal: use contemporary published studies that involved the use of currently used BMS; provide all the assumptions and justifications in driving a performance goal; and adjust event rates to the proportion of the protocol mandating angiography, before deriving a performance goal.

For these clinical studies, the primary endpoint should be the nine-month target vessel failure, according to Fronczak. The secondary endpoint must include target lesion failure, along with any major adverse coronary events. The agency also is now requesting the inclusion of any angiographic endpoints. For angiographic follow-up, a subset of angio patients will generally be needed, especially for new stent design.

"We expect there to be a greater than 80 percent follow up in angio patients, which should be timed for some point after the nine-month clinical assessment point," Fronczak said. "We also recommend the use a core lab in evaluating angio.

"Our current thinking on global clinical trials is that they are acceptable, as long as they include a portion of U.S. sites, and as long as the study population is applicable to the U.S. population and U.S. clinical practice," she noted.